Release of β‐Amyloid from High‐Density Platelets

Abstract

The main component of Alzheimer's disease (AD) senile plaques in the brain is amyloid-beta peptide (Abeta), a proteolytic fragment of the amyloid precursor protein (APP). Platelets contain both APP and Abeta and much evidence suggests that these cells may represent a useful tool to study both amyloidogenic and nonamyloidogenic pathways of APP processing. It has been demonstrated that platelets activated by physiological agonists, such as thrombin and collagen, specifically secrete Abeta ending at residue 40. To verify whether APP beta-processing could be observed also in an in vitro system of highly concentrated platelets, we measured the Abeta released in the incubation media of 5 x 10(9) platelets/mL by enzyme-linked immunosorbent assay (ELISA). The activation status of platelets was investigated by ultrastructural analysis. We found that Abeta(40) levels were significantly higher in incubation media of 5 x 10(9)/mL platelets in comparison with 10(8)/mL platelets (normalized values), while Abeta(42) levels were not affected by cell density. The ultrastructural analysis showed platelets at different phases of activation: some platelets were at earlier stage, characterized by granule swelling and dilution, others had granules concentrated in a compact mass in the cell centers within constricted rings of circumferential microtubules (later stage). Normally concentrated cells had the characteristic morphology of resting platelets. Our data suggest that high-density platelets undergo activation likely by increased frequency of platelet-platelet collisions. This, in turn, determines the activation of APP beta-processing with consequent release of Abeta(40). Investigating the biochemical pathways triggering Abeta secretion in platelets might provide important information for developing tools to modulate this phenomenon in AD brains.

The Vitamin Nicotinamide: Translating Nutrition into Clinical Care

“…Apoptosis can contribute to disorders such as diabetes [13,14,15,16], tissue ischemia [17,18,19,20], bone fatigue [21], Alzheimer's disease [22,23,24,25,26,27,28,29,30,31,32], neurodegenerative disorders [33,34,35,36], plasticity associated with ischemic preconditioning [37], aging-related diseases [38,39,40], and toxic conditions during development [41,42]. The pathology with these disorders can be linked to mitochondrial dysfunction [43,44,45,46], especially during metabolic disorders [47] and Alzheimer’s disease [48], that ultimately can lead to cell death in a variety of cells such as neurons, endothelial cells (ECs), cardiomyocytes, and smooth muscle cells [32,49,50,51,52,53].…”

Platelet biomarkers in Alzheimer’s disease

“…In fact, a recent study indicated that soluble Aβ can be internalized into lysosomes by the cerebrovascular smooth muscle cells, yielding Aβ deposits within the extracellular space of the vessel wall upon degeneration of smooth muscle cells. This is supposedly an important mechanism leading to cerebral amyloid angiopathy in AD [16] . Early studies by Di Luca et al [17] and Rosenberg et al [18] showed a reduction in the ratio between larger (120 to 130 kDa) and smaller (110 kDa) specimens of sAPP in platelets of patients with AD.…”

High Serum Aβ and Vascular Risk Factors in First-Degree Relatives of Alzheimer’s Disease Patients

“…There is a growing consensus that changes in blood Aβ levels parallel AD onset and progression, although these findings remain discrepant with respect to specific species, that is, Aβ or Aβ 1-40 (2)(3)(4)(5)(6). Despite this discrepancy, evidence is now emerging in favor of the more pathologic form, Aβ , being elevated at the stage of mild cognitive impairment or an even earlier prodromal stage of AD, possibly owing to increased production (2,5,7).…”